Many women diagnosed with early-stage breast cancer with a high risk of recurrence (the cancer coming back) get chemotherapy after surgery to reduce the risk of recurrence. In some cases, the chemotherapy may be given on a dose-dense schedule.

Dose-dense chemotherapy means that the chemotherapy medicines are given every 2 weeks, instead of the standard schedule of every 3 weeks. Doctors may recommend a dose-dense regimen for some women because other research has shown that this approach can improve survival and decrease the risk of recurrence more effectively than a standard chemotherapy schedule.

In many cases, dose-dense chemotherapy can cause anemia.

Anemia means you have a low red blood cell count or your red blood cells don’t have enough hemoglobin. Hemoglobin is an iron-rich protein found in red blood cells that carries oxygen from your lungs to the rest of your body. If you’re anemic, you might feel tired, weak, cold, or dizzy. You also may bruise easily and have frequent nosebleeds.

Erythropoietin (EPO) medicines such as Epogen (chemical name: epoetin alfa) and Procrit (chemical name: epoetin alfa) can help your body make more red blood cells. But it hasn’t been clear if giving EPO to women being treated for early-stage breast cancer made sense because earlier studies had shown that it led to more recurrence and worse survival, as well as a higher risk of blood clots.

For these reasons, the U.S. Food and Drug Administration (FDA) said that EPO should be used only to treat anemia caused by chemotherapy. The FDA also said that EPO shouldn’t be used to prevent anemia or used when the outcome of a treatment is cure, such as when chemotherapy is used to treat early-stage breast cancer.

Now, a new study has found that EPO effectively prevented anemia in women who were getting dose-dense chemotherapy to treat early-stage breast cancer with a high risk of recurrence with no effect on recurrence or survival. Still, the women who got EPO were more than twice as likely to have blood clots compared to women who didn’t get EPO.

These new EPO study results are part of an earlier German study looking at two chemotherapy regimens to treat early-stage breast cancer with a high risk of recurrence. Both regimens used Ellence (chemical name: epirubicin), Cytoxan (chemical name: cyclophosphamide), and Taxol (chemical name: paclitaxel). Nearly 1,300 women diagnosed with stage II to stage IIIA breast cancer with at least four positive lymph nodes were randomly assigned to get either:

the standard regimen: four 3-week cycles of 90 mg of Ellence and 600 mg of Cytoxan followed by four 3-week cycles of 175 mg of Taxol (626 women)

the dose-dense regimen: three 2-week cycles of 150 mg of Ellence, followed by three 2-week cycles of 225 mg of Taxol, followed by three 2-week cycles of 2,500 mg of Cytoxan (658 women)

After 10 years of follow-up, the study showed that women who got the dose-dense regimen standard regimen had better survival than the women who got the standard regimen.

The women who got the dose-dense regimen also had a high rate of transfusions because their hemoglobin rates dropped too low (below 9 g/dL – grams per deciliter of blood).

For the EPO study, the researchers randomly assigned the women getting the dose-dense regimen to get either:

three injections of EPO weekly to maintain a hemoglobin level of 12.5 to 13 g/dL; the EPO injections were stopped if hemoglobin levels were higher than 14 and started again if they dropped below 13 g/dL (324 women)

no EPO (319 women)

All the women who got the dose-dense regimen also took 200 mg of iron per day.

The researchers found that women who got EPO were much less likely to need a transfusion because of low hemoglobin levels:

86 women (28.1%) who didn’t get EPO had a transfusion

41 women (12.8%) who got EPO needed a transfusion

Relapse-free survival rates (the length of time the women lived without a recurrence) after 5 years were similar for the two groups:

71% for the women who didn’t get EPO

72% for women who got EPO

Overall survival rates (the length of time the women lived, whether or not the cancer came back) after 5 years, also were similar between the two groups:

83% for the women who didn’t get EPO

81% for the women who got EPO

But the women who got EPO were almost twice as likely to have a blood clot as women who didn’t get EPO:

39 women (13%) who got EPO had a blood clot

22 women (7%) who didn’t get EPO had a blood clot

While these results are promising, not all doctors are sure that EPO is a good choice to prevent anemia in women getting dose-dense chemotherapy for early-stage, high-risk breast cancer. Some doctors felt that the study wasn’t set up to really see if EPO affected relapse-free survival or overall survival. Other doctors said that using a slightly lower dose of Cytoxan in the dose-dense regimen would offer the same treatment benefits while keeping hemoglobin levels steady. This would reduce the need for transfusions, which would eliminate the need for EPO.

Also, Ellence is more commonly used in Europe, so the study may not affect standards of care in the United States. A typical U.S. dose-dense chemotherapy regimen is more likely to involve Adriamycin (chemical name: doxorubicin) and Cytoxan, followed by Taxol.

If you’re getting chemotherapy, especially dose-dense chemotherapy, after surgery to remove early-stage breast cancer with a high risk of recurrence, talk to your doctor about your risk of anemia. Also ask about your risk of blood clots. Together, you and your doctor can decide on the best treatments to lower your risk of the breast cancer coming back as well as steps you can take to reduce your risk of anemia.

Visit the Breastcancer.org Chemotherapy section to learn more about dose-dense chemotherapy and chemotherapy side effects.